[Contribution of FreeStyle Libre® in the care of diabetic patients : experience at the CHU of Liege]. / L'apport du système FreeStyle Libre® dans la prise en charge du patient diabétique : expérience au CHU de Liège.

Since July 2016, diabetic patients included in the INAMI glycemic self-monitoring system in category A in Belgium can benefit from a new system for measuring the concentration of subcutaneous glucose : FreeStyle Libre® (FSL) from Abbott company. The main advantage of this technology is that it is less invasive as it does not require finger blood sampling and allows patients to obtain, in addition to the instantaneous value of glucose concentration, retrospective kinetic data, but also prospective trend of its kinetics. In this study, we mainly evaluated the contribution of FSL on the overall equilibration of diabetes and on the time spent in hypoglycaemia. We also asked patients how satisfied they were with this system. Data from 838 diabetic patients (type 1 or total insulin deficiency) were collected between May 2016 and October 2017, 645 patients with FSL system and 193 preferring to continue self-monitoring of capillary blood glucose (SBG). In the FSL group, compared to the SBG group, there was a slight decrease in HbA1c estimated at 0.15 ± 0.073 % after 15 months. This decrease appears mainly when the starting level is high (HbA1c superior to 7.5 %). Patients perform an average of 8.8 checks per day : the more patients perform daily scans, the greater the number of data comprised within the target, that is, the better the overall glucose control. A higher number of scans is also associated with a decrease in the average duration of hypoglycaemia. Finally, the satisfaction survey shows a high degree of patient satisfaction with the use of FSL.

Depuis juillet 2016, les patients diabétiques inclus dans la convention d'auto-surveillance glycémique de l'INAMI en catégorie A en Belgique peuvent bénéficier d'un nouveau système de mesure de la concentration du glucose sous-cutané : le FreeStyle Libre® (FSL) de la société Abbott. L'avantage principal de cette technologie est qu'elle est moins invasive puisqu'elle ne nécessite pas de prélèvement sanguin et qu'elle permet aux patients d'obtenir, outre la valeur instantanée de la concentration de glucose, des données cinétiques rétrospectives, mais aussi une tendance prospective de son évolution. Dans cette étude rétrospective, nous avons évalué principalement l'apport du FSL sur l'équilibration du diabète et sur le temps passé en hypoglycémie. Nous avons également interrogé les patients sur leur degré de satisfaction vis-à-vis de ce système. Les données de 838 patients diabétiques (type 1 ou totalement insulinoprives) ont été collectées entre mai 2016 et octobre 2017, 645 patients porteurs du système FSL et 193 préférant poursuivre une auto-surveillance de la glycémie capillaire (ASG). On observe dans le groupe FSL, par rapport au groupe ASG, une légère diminution du taux d'HbA1c évaluée à 0,15 ± 0,073 % après 15 mois. Cette diminution apparaît principalement lorsque le niveau de départ est élevé (HbA1c sup�rieur a 7,5 %). Les patients porteurs du FSL réalisent en moyenne 8,8 contrôles quotidiens : plus les patients effectuent de scans journaliers, plus le nombre de données comprises dans la cible augmente, c'est-à-dire meilleur est l'équilibre glycémique. Un nombre plus élevé de scans est également associé à une diminution de la durée moyenne des hypoglycémies. Enfin, l'enquête de satisfaction démontre, dans l'ensemble, un haut degré de satisfaction des patients par rapport à l'usage du FSL.

Plasma Insulin Levels and Hypoglycemia Affect Subcutaneous Interstitial Glucose Concentration.

BACKGROUND: Continuous glucose monitoring (CGM) accuracy during hypoglycemia is suboptimal. This might be partly explained by insulin or hypoglycemia-induced changes in the plasma interstitial subcutaneous (SC) fluid glucose gradient. The aim of the present study was to assess the role of plasma insulin (PI) and hypoglycemia itself in the plasma and interstitial SC fluid glucose concentration in patients with type 1 diabetes mellitus. METHODS: Eleven subjects with type 1 diabetes (age 36.5 ± 9.1 years, HbA1c 7.9 ± 0.4% [62.8 ± 2.02 mmol/mol]; mean ± standard deviation) were evaluated under hyperinsulinemic euglycemia and hypoglycemia. Each subject underwent two randomized crossover clamps with either a primed 0.3 (low insulin) or 1 mU/(kg·min) (high insulin) insulin infusion. The raw CGM signal was normalized with median preclamp values to obtain a standardized measure of the interstitial glucose (IG) concentration before statistical analysis. RESULTS: The mean PI concentration was greater in high insulin studies (HISs) versus low insulin studies (LISs) (412.89 ± 13.63 vs. 177.22 ± 10.05 pmol/L). During hypoglycemia, glucagon, adrenaline, free fatty acids, glycerol, and beta-OH-butyrate were higher in the LIS (P < 0.0001). Likewise, the IG concentration was significantly different (P < 0.0001). This was due to lower IG concentration than plasma glucose (PG) concentration during the euglycemic hyperinsulinemic phases in the HIS. In contrast, no difference was observed during hypoglycemia. This was the result of an unchanged PG/IG gradient during the entire LIS, while in the HIS, this gradient increased during the hyperinsulinemic euglycemia phase. CONCLUSION: Both PI levels and hypoglycemia affect the relationship between IG and PG concentration. ClinicalTrials.gov Identifier: NCT01714895.

The Benefits and Limits of Technological Advances in Glucose Management Around Physical Activity in Patients Type 1 Diabetes.

Physical activity is highly recommended for patients living with type 1 diabetes (T1D) due to its varied health benefits. Nevertheless, glucose management, during and in the hours following exercise, represents a great challenge for these patients who most often end up leading a sedentary life style. Important technological advances in insulin delivery devices and glucose monitoring are now available and continue to progress. These technologies could be used to alleviate glucose management related to physical activity in T1D. Continuous glucose monitoring (CGM) helps patients observe the trends of glycemic fluctuations when exercising and in the following night to deal pre-emptively with hypoglycemic risks and treat hypoglycemic episodes in a timely manner. Insulin pumps offer the flexibility of adjusting insulin basal rates and boluses according to patient's specific needs around exercise. The artificial pancreas links CGM to pump through an intelligent hormone dosing algorithm to close the loop of glucose control and has thus the potential to ease the burden of exercise in T1D. This review will examine and discuss the literature related to physical activity practice using each of these technologies. The aim is to discuss their benefits as well as their limitations and finally the additional research needed in the future to optimize their use in T1D.

Hypoglycemic and anti-hyperglycemic study of Ocimum tenuiflorum L. leaves extract in normal and streptozotocin-induced diabetic rats

Objective To investigate the antidiabetic activity of Ocimum tenuiflorum L. (O. tenuiflorum) leaves used in the traditional medicine management of diabetes in Malaysia. Methods O. tenuiflorum leaves were extracted sequentially with hexane, chloroform, ethyl acetate, methanol, and water. The extracts were evaluated in terms of antidiabetic activity by using acute, subcutaneous glucose tolerance, and sub-chronic tests in streptozotocin-induced diabetic rats. The extracts were also subjected to phytochemical analyses. Results With an acute dose (1 g/kg), the methanol extracts showed significant reduction (31%) in fasting blood glucose (FBG) of the streptozotocin-induced diabetic rats. The FBG-decreasing effect of ethyl acetate extract was more rapid than that of the other extracts; the decreasing rates were 20% after 2 h, 21% after 3 h, and 8% after 5 and 7 h. After 7 h (31%), the effect of methanol extract on FBG was significantly lower than that of metformin. In the subcutaneous glucose tolerance test, only methanol and hexane extracts showed the similarity of metformin in diabetic rats. After 14 days, the effects of these extracts were similar to those of metformin (63.33%). The total flavonoid and phenolic contents of extracts decreased as the polarity of the extraction solvent increased. Conclusions The results obtained provide support for a possible use of O. tenuiflorum leaves in managing hyperglycemia and preventing the complications associated with it in type 2 diabetic.

Glycaemic load versus carbohydrate counting for insulin bolus calculation in patients with type 1 diabetes on insulin pump.

AIMS: To evaluate feasibility and effectiveness on short-term blood glucose control of using glycaemic load counting (GLC) versus carbohydrate counting (CC) for prandial insulin dosing in patients with type 1 diabetes (T1D). METHODS: Nine T1D patients on insulin pump, aged 26-58 years, HbA1c 7.7 ± 0.8 % (61 ± 8.7 mmol/mol), participated in this real-life setting study. By a crossover design, patients were randomised to calculate their pre-meal insulin dose based on the insulin/glycaemic load ratio (GLC period) or the insulin/carbohydrate ratio (CC period) for 1 week, shifting to the alternate method for the next week, when participants duplicated their first week food plan. Over either week, a blind subcutaneous continuous glucose monitoring was performed, and a 7-day food record was filled in. RESULTS: Total daily insulin doses (45 ± 10 vs. 44 ± 9 I.U.; M ± SD, p = 0.386) and basal infusion (26 ± 7 vs. 26 ± 8 I.U., p = 0.516) were not different during GLC and CC periods, respectively. However, the range of insulin doses (difference between highest and lowest insulin dose) was wider during GLC, with statistical significance at dinner (8.4 ± 6.2 vs. 6.0 ± 3.9 I.U., p = 0.041). Blood glucose iAUC after lunch was lower, albeit not significantly, during GLC than CC period (0.6 ± 8.6 vs. 3.4 ± 8.2 mmol/l∙3 h, p = 0.059). Postprandial glucose variability, evaluated as the maximal amplitude after meal (highest minus lowest glucose value), was significantly lower during GLC than CC period at lunch (4.22 ± 0.28 vs. 5.47 ± 0.39 mmol/l, p = 0.002) and dinner (3.89 ± 0.33 vs. 4.89 ± 0.33, p = 0.026). CONCLUSIONS: Calculating prandial insulin bolus based on glycaemic load counting is feasible in a real-life setting and may improve postprandial glucose control in people with T1D.

Time lag of glucose from intravascular to interstitial compartment in type 1 diabetes.

The premise of effective closed-loop insulin therapy for type 1 diabetes (T1D) relies on the accuracy of continuous interstitial fluid glucose sensing that represents the crucial afferent arm of such a system. An important determinant of sensor accuracy is the physiological time lag of glucose transport from the vascular to the interstitial space. The purpose of current studies was to determine the physiological time lag of glucose transport from the vascular to the abdominal subcutaneous interstitial space in T1D. Four microdialysis catheters were inserted into the abdominal subcutaneous space in 6 T1D subjects under overnight fasted conditions. Plasma glucose was maintained at 113.7 ± 6.3 mg/dl using a continuous intravenous insulin infusion. After sequential intravenous bolus administrations of glucose isotopes, timed plasma and interstitial fluid samples were collected chronologically and analyzed for tracer enrichments. We observed a median (range) time lag of tracer appearance (time to detection) into the interstitial space after intravenous bolus of 6.8 (4.8-9.8) minutes, with all participants having detectable values by 9.8 minutes. We conclude that in the overnight fasted state in T1D adults, the delay of glucose appearance from the vascular to the interstitial space is less than 10 minutes, thereby implying that this minimal physiological time lag should not be a major impediment to the development of an effective closed-loop control system for T1D.

Hypoglycemic and anti-hyperglycemic study of Gynura procumbens leaf extracts.

OBJECTIVE: To study the antidiabetic activity of Gynura procumbens (G. procumbens) used in the traditional management of diabetes in Southern Asia. METHODS: G. procumbens leaves were extracted sequentially with graded percentage of ethanol in water (95%, 75%, 50%, 25% and 0%), and the extracts were tested for antidiabetic activity using acute (7 h), subcutaneous glucose tolerance test and sub-chronic (14 d) test in non-diabetic and streptozotocin-induced diabetic rats. The extracts were further subjected to phytochemical studies. RESULTS: In acute dose (1 g/kg), the extracts significantly lowered fasting blood glucose (FBG) in streptozotocin-induced diabetic rats (P<0.05). However, the FBG-lowering effect of the 25% extract compared to the other extracts, was rapid (47% after 2 h) and the highest: 53%, 53% and 60% in the 3rd, 5th, and 7th h, respectively (P<0.05), comparable only to the effect of metformin. Furthermore, the extracts suppressed peak FBG in subcutaneous glucose tolerance test, but only the 0% and 25% extracts, and metformin sustained the decrease until the 90th min (P<0.05). Moreover, in the 14 days study, the 25% extract exerted the highest FBG-lowering effect, namely 49.38% and 65.43% on days 7 and 14, respectively (P<0.05), similar to the effect of metformin (46.26% and 65.42%). Total flavanoid and phenolic contents in the extracts were found to decrease with increase in polarity of extraction solvents. The composition of reference compounds (chlorogenic acid, rutin, astragalin and kaempferol-3-O-rutinoside) followed a similar trend. CONCLUSIONS: G. procumbens contains antidiabetic principles, most extracted in 25% ethanol. Interaction among active components appears to determine the antidiabetic efficacy, achieved likely by a metformin-like mechanism.

Hypoglycemic and anti-hyperglycemic study of Gynura procumbens leaf extracts

<p><b>OBJECTIVE</b>To study the antidiabetic activity of Gynura procumbens (G. procumbens) used in the traditional management of diabetes in Southern Asia.</p><p><b>METHODS</b>G. procumbens leaves were extracted sequentially with graded percentage of ethanol in water (95%, 75%, 50%, 25% and 0%), and the extracts were tested for antidiabetic activity using acute (7 h), subcutaneous glucose tolerance test and sub-chronic (14 d) test in non-diabetic and streptozotocin-induced diabetic rats. The extracts were further subjected to phytochemical studies.</p><p><b>RESULTS</b>In acute dose (1 g/kg), the extracts significantly lowered fasting blood glucose (FBG) in streptozotocin-induced diabetic rats (P<0.05). However, the FBG-lowering effect of the 25% extract compared to the other extracts, was rapid (47% after 2 h) and the highest: 53%, 53% and 60% in the 3rd, 5th, and 7th h, respectively (P<0.05), comparable only to the effect of metformin. Furthermore, the extracts suppressed peak FBG in subcutaneous glucose tolerance test, but only the 0% and 25% extracts, and metformin sustained the decrease until the 90th min (P<0.05). Moreover, in the 14 days study, the 25% extract exerted the highest FBG-lowering effect, namely 49.38% and 65.43% on days 7 and 14, respectively (P<0.05), similar to the effect of metformin (46.26% and 65.42%). Total flavanoid and phenolic contents in the extracts were found to decrease with increase in polarity of extraction solvents. The composition of reference compounds (chlorogenic acid, rutin, astragalin and kaempferol-3-O-rutinoside) followed a similar trend.</p><p><b>CONCLUSIONS</b>G. procumbens contains antidiabetic principles, most extracted in 25% ethanol. Interaction among active components appears to determine the antidiabetic efficacy, achieved likely by a metformin-like mechanism.</p>